JUNE1967
NOTES
1999
Registry No.-Ia, 10476-70-7; Ib, 10476-71-8; IC, 10476-72-9; Id, 10476-73-0; Ie, 10476-74-1; cis IIa, 10476-75-2; trans IIa, 10476-76-3; cis IIb, 10476-77-4; trans IIb, 10476-78-5; cis IIc, 10476-79-6; VI, 1047680-9. Acknowledgment.-The author is indebted to the National Science Foundation for partial support of this project from Grant GP 5945.
VI ethyl benzoate (VII). The structure of VI1 was established by unequivocal synthesis according to Scheme 11, SCHEME I1
Reissert Compound Studies. XVI. Reaction of 2-Benzoyl-1,2-dihydroisoquinaldonitrile with Lactones' CN JOHNhl. W E F E RAND ~ FRANK D. POPP
COCH,
Ix
VIII
Department of C'hemistry, Clarkson College of Technology, Potsdam, New York
HCOH I
Received December $8,1966
We have recently reported1v3that the Reissert anion (I) can be conveniently generated at room temperature using sodium hydride in dimethylformamide. We now wish to report use of this system in two novel reactions of 2-benzo yl-l ,2-dihydroisoquinaldonitrile(11) with p-propiolactone and 0-butyrolactone.
I
II
Reaction of I1 with p-propiolactone and sodium hydride in dimethylformamide led to the formation of p-(1-isoquinoly1)ethyl phenyl ketone (111). Formation of I11 can be rationalized according to Scheme I. Opening of the lactone by I followed by rearrangement of IV and decarboxylation gives rise to 111. The structure of I11 was confirmed by an alternative synthesis from the anion I1 and p-bromopropiophenone. This alkylation gave an intermediate corresponding in composition to the enol ester V or diketone VI; alkaline hydrolysis of this substance led to 111. Reaction of I1 with p-butyrolactone did not produce a simple homolog of I11 but rather 1-(1-isoquinoliny1)SCHEME
1
Iv
(1) Part XV: F . D. Popp and J. M. Wefer, J . Heterocyclic Chem.. in press. (2) U. S. Public Health Service Predoctoral Fellow (I-Fl-GM-25,896) from Institute of General Medical Sciences. (3) F. D. POPPand J. M. Wefer, Chem. Commun., 207 (1966).
CHsCHOCC6Hs
II
CH3
X
0 VII
and by low temperature4 condensation of I1 with acetaldehyde, which also gave VII. Any mechanism (analogous to Scheme I) in which the anion I cleaves the lactone ring as a first step toward the formation of VI1 suffers from the disadvantage that the lactone must be opened in an unusual fashion (ie., cleavage of a carbon-carbon bond), and that a twocarbon fragment must be eliminated prior to or during the rearrangement step. Since VI1 was also formed by condensation of I1 with acetaldehyde and since acetaldehyde could be detected when P-butyrolactone was treated with sodium hydride in dimethylformamide (albeit in low yield), it may be that I1 actually reacts with acetaldehyde formed in situ. The greater steric hindrance to nucleophilic attack by I at the @-carbonof P-butyrolactone relative to P-propiolactone causes the reaction to follow a different pathway, initiated by nucleophilic attack by hydride at the lactone carbonyl, leading to the cleavage into what appear to be two molecules of acetaldehyde. The fact that VI1 is obtained in much higher yield than is acetaldehyde (in the absence of I) can be accounted for by the immediate reaction of I with acetaldehyde while in the absence of I the acetaldehyde can undergo other basecatalyzed reactions. Treatment of I1 with either y-butyro-, y-valero-, or y-decalactone and sodium hydride in dimethylformamide gave only 1-benzoylisoquinoline indicating that five-membered lactones are either too stable to react under these conditions or react too slowly to compete with the rearrangement to the For purposes of comparison the above reactions were attempted using phenyllithium in ether-dioxane at -2Oo.*J I n all cases tried (p-propio-, P-butyro-, and y-valerolactone) starting Reissert compound (11) was recovered. (4) L. R. Wslters. N. T. h e r . and W. E. MoEwen, J . Am. Chem. Soc., 80, 1177 (1968). (5) V. Boekelheide and J. Weinstock, ibid., 74, 660 (1952).
VOL. 32
NOTES
2000 Experimental Section6
with 5 g of 30% sodium hydride in oil while a stream of nitrogen was percolated through the mixture and into a reagent solution of 2,4-dinitrophenylhydrazine. I n this manner low yields of acetaldehyde-2,4-dinitrophenylhydrazone(mp 144-146') were obtained. The reaction was accompanied by the generation of considerable heat and polymer formation.
Reaction of I1 with p-Propiolactone (Preparation of 111).-2Benzoyl-l,2-dihydroisoquinaldonitrile(11) (0.01 mole) and 0propiolactone (0.02 mole) were dissolved in 40 ml of dimethylformamide and 30% sodium hydride in oil (0.01 mole) was added to the stirred solution. After 1.5 hr stirring the mixture was poured onto 500 g of ice and filtered after standing. A solid Registry No.-11, 844-25-7; 111, 10293-89-7; picrate (mp 104-109") was obtained and recrystallized from hexane to of 111, 10293-90-0; 2,4dinitrophenylhydrazone of 111, 1730 and 1665 cm-1). give a 19% yield of 111, mp 111-112' A(: 10293-91-1; V, 10293-92-2; picrate of V, 10293-93-3; Anal. Calcd for ClsHlbNO: C, 82.73; H I 5.79; N, 5.36. Found: C, 82.47; H I 6.03; N, 5.26. VI, 10293-94-4; picrate of VI, 10293-95-5; VII, 10293A picrate (mp 202-204') from ethanol, was prepared. 96-6; picrate of VII, 10293-97-7; VIII, 1198-30-7. Anal. Calcd for C24HlsN4O8: C, 58.78; H , 3.70; N, 11.43. Found: C, 58.83; H , 3.81; N, 11.32. The 2,4-dinitrophenylhydrazoneof I11 was prepared (mp 192-193 ") from ethanol-dimethylformamide. Anal. Calcd for CuH1gN504: C, 65.30; H, 4.34; N, 15.87. a-Halo Ketones. IV.' Reductive Found: C, 65.42; H , 4.91; N, 15.98. Dehalogenation by Substituted Pyridines Preparation of 111.-Reaction of 0.01 mole of I1 with 0.01 mole of p-bromopropiophenone and sodium hydride in dimethylformamide as above afforded a gum in 68% yield. RecrystallizaE. W. WARNHOFF AND D. R. MARSH ALL^ tion from hexane-ethyl acetate gave a good recovery of solid (V or VI), mp 172-172.5' A(: 1740, 1700, 1630, 835 cm-1). Department of Chemistry, University of Western Ontario, Anal. Calcd for C25H1gN02: C , 82.17; H I 5.24; N, 3.83. London, Ontario, Canada Found: C, 81.80; H, 5.43; N, 3.59. A picrate (mp 163-164') from ethanol, was prepared. Anal. Calcd for C31H2&09: C, 62.73; H, 3.57; N, 9.44. Received December 19, 1966 Found: C, 62.52; H , 3.58; N, 9.27. The crude intermediate ( V or VI) obtained above (2.0 g) was In part I1 of this series3 the reaction of a typical reeuxed for 1.5 hr in 50 ml of 50% ethanol containing 8 g of cyclic a-halo ketone, 2a-bromocholestan-3-one (partial potassium hydroxide. Dilution with water and filtration gave a structure l ) , with a variety of alkyl-substituted pyriwhite solid (mp 108-109') in 887, yield. Recrystallization from hexane gave mp 111-112'. This material was identical dines was examined. It was found that, in addition to compound I11 as demonstrated by mixture melting point and to dehydrobromination (with and without rearrangeinfrared spectra. ment) and displacement, reductive debromination to Reaction of I1 with 0-Butyrolactone (Preparation of VII) .-The cholestan-3-one (partial structure 2) occurred. Acreaction was carried out as described above for p-propiolactone on a 0.01 molar scale. A white solid was isolated and recrystalcurate analysis for the reduction product was complilized from hexane-ethyl acetate to give a 50% yield, mp 85-86" cated both by the fact that the starting bromo ketone ( A E r 1755 and 1665 em-'). Anal. Calcd for (>l&bN02: C, 77.96; H I 5.48; N, 5.05. Found: C, 78.13; H , 5.48; N, 5.08. A picrate (mp 204-205') from ethanol, was prepared. Anal. Calcd for C24HlaN409: C, 56.92; H, 3.58; N, 11.06. 0 H H H Found: C, 56.88; H , 3.64; N, 11.20. I-( 14soquinolinyl)ethyl Benzoate (VII) .-To a stirred solution of 0.02 mole of 2-benzenesulfonyl-l,2-dihydrois~quinaldonitrile~ 1 2 3 4 in 80 ml of dimethylformamide was added 0.02 mole of 3070 sodium hydride in oil. After 1 hr the mixture was poured onto 500 g of ice and isoquinaldonitrile (VIII) (80%) (mp 86-88') was discovered to contain 12% of 2, and by the anwas collected. Without further purification VI11 was treated alytical method. The difficulty in separating a small with methyl magnesium iodide as reported8 to give l-acetylisoamount of 2 from a large amount of 3 made it most conquinoline (IX) as a yellow oil in 72% yield (A:Z 1700 and 1625 venient to estimate cholestan-3-one as the remainder cm-1). Compound I X (0.0115 mole) was dissolved in 30 ml of after Al- and A4-cholesten-3-one (partial structures 3 methanol and 0.25 g of sodium borohydride was added with stirring. After 0.5 hr the mixture was poured onto ice and and 4) had been determined from tlc spot intensities extracted with methylene chloride. 1-(1-1soquinolinyl)ethanol and ultraviolet measurements. (X) was isolated in 91y0 yield as an oil from the dried (NazSOh) In a subsequent paper, Nace and Iacona4 repeated organic phase (A:$ 3400 and 1630 cm-l). The oil (X) (0.0097 the reaction of 7-collidine with pure 1 from which the mole) was refluxed with 1.8 g (0.0129 mole) of benzoyl chloride in 50 ml of pyridine for 1 hr. After being poured onto ice, 2.61 contaminating cholestan-&one had been removed by g (97Yc) of white solid was collected. Recrystallization from chromatography on silica gel. A shoulder correspondhexane-ethyl acetate gave mp 87-88', This material was ing to cholestan-&one was observed in the glpc chroidentical with T'II prepared from p-butyrolactone as demonstrated matogram and infrared spectrum of the reaction by mixture melting point and infrared spectra. product, but it was claimed that the saturated ketone Condensation of I1 with Acetaldehyde.-Acetaldehyde and I1 were reacted with phenyllithium in ether-dioxane a t -20' as amounted to less than 2% of the total product. The reported for other aldehyde^.^ A solid (mp 85-87') from hexaneauthors concluded that "the reduction reaction is not ethyl acetate, was isolated in 60% yield. This material was significant in the reaction of bromo ketones with identical with VI1 as demonstrated by mixture melting point ~ollidine."~Although the yields (20-46%) of cholesand infrared spectra. Treatment of p-Butyrolactone with Sodium Hydride.+tan-3-one reported in our earlier work3 were admitted Butyrolactone ( 5 g) in 100 ml of dimethylformamide was treated to be subject to cumulative error, it was certain that
Br-xx}-od} +oa}+
more than 2% of 2 was produced in the 7-collidine re(6) All melting points are corrected.
Analyses were by Spang Microanalytical Laboratory, Ann Arbor, Mich. We wish t o thank the Tennessee Eastman Co. for a sample of 8-butyrolactone. ( i )J. M . Wefer, A. Catala, and F. D. Popp, J . Ore. Chem., 80,3075 (1965). (8) A. Kaufmann, P . Ilandliker, and H. Burkhardt, Ber., 46, 2929 (9113).
(1) Part 111: E.W.Warnhoff, J . Ore. Cham., 28, 887 (1963) (2) Province of Ontario Graduate Fellow, 1966-1967. (3) E . W.Warnhoff, J . Ore. Chem., 21, 4587 (1962). (4) H.R.Nace and R. N. Iaoona, ibid., 39, 3498 (1964).
